Many naturally-occurring or synthetic chemicals are known or suspected etiological agents for cancer, genetic defects, or reproductive effects. Rodents bearing reporter transgenes such as lacI in Big Blue mice and rats or lacZ in Muta(TM) Mouse were developed to enable the detection and analysis of mutations in various target organs. Additionally, second generation transfenic animal systems are needed, particularly model systems of relatively low cost, technical simplicity, and with the ability to quantitatively estimate germ cell mutations. The utility of the mouse model carrying the shuttle vector phiX174 am3 cs70 as an in vivo and ex vivo will be evaluated in Phase I. Mice hemizygous for the shuttle vector will be bred and exposed to the mutagen N-ethyl-N-nitrosourea (ENU) as weanlings and sacrificed six weeks later in order to obtain information on the induced mutational effects on the spermatogonial stem cell population. Methods for distinguishing revertants caused by DNA lesions which are fixed as mutations in vivo from lesions which are fixed as mutations during the rescue of the shuttle vector will be identified.